This invention is directed to a process for preparing pyridine-2,3-dicarboxylic acid by the oxidation of quinoline. The invention is more particularly directed to a process for preparing that acid by oxidizing quinoline with a chlorate salt in an aqueous acid medium. The acid is useful as an intermediate in the preparation of various herbicides and pharmaceuticals, and in the preparation of dye intermediates.
Pyridine-2,3-dicarboxylic acid, also known as quinolinic acid, has been prepared from quinoline and its derivatives by well established means. The chemical processes heretofore used, however, have not been economical on a commercial scale because of low yield, high raw material cost, or severe process conditions necessary to achieve a commercially acceptable rate or yield.
The oxidation of quinoline or a quinoline derivative by common chemical oxidants is well known in the art. Oxidation by potassium permanganate is disclosed, for example, in Current Sci. 13 206-7, 1944; Ber. 65B, 11-13, 1932; Anal. Chem. 23 535-6, 1951; Chemical Abstracts 50 9996, 52 11847d, 55 530e 56 5807i, 99 141522c. Oxidation by manganese dioxide is shown in U.S. Patent 2,392,437 and U.K. Pat. No. 596,230. Chromic and lead oxides have also been employed (J.A.C.S. 70, 3827-30, 1948; German Pat. No. 1,071,085; Chemical Abstract 47 5232c).
The oxidation of quinoline and quinoline derivatives by nitric acid or nitrogen oxides, in either liquid or vapor phase, has also been extensively developed. See, for example, U.S. Pat. Nos. 2,396,457; 2,475,969; 2,505,568; 2,513,251; 2,513,099; Ger. Nos. 912, 216; 1.133,714; 1.161,563; and Chemical Abstract 44 3494e, 50 9403e. The process conditions required in these procedures, however, are normally so severe that nicotinic acid is the main or only product.
Quinoline and quinoline derivatives have also been oxidized by ozonation, but the products require further chemical oxidation to produce pyridine dicarboxylic acid. Such procedures are disclosed in J.A.C.S. 71 3020, 1949; U.S. Pat. No. 2,964,529; CA 69 35876s; CA 88 225606; and CA 69 2825w.
The electrochemical oxidation of quinoline and its derivatives has been successfully demonstrated (J.A.C.S. 68 2472-3, 1946; U.S. Pat. Nos. 2,453,701; 2,512,483; ) but the procedures have not been of commercial significance, usually because of the cost involved in operation of this complex procedure. More practical procedures, using hydrogen peroxide to oxidize quinoline in an aqueous acid medium, are shown in Eur. Pat. Appln. Nos. 024,197 and 034,943; CA 50 12057b; CA 60 15704c; and U.S. Pat. Nos. 2,371,691. Catalytic oxidations of quinoline using oxygen or air are also known (U.S. Pat. No. 3,829,432; Ger. Pat. No. 1,010,524; CA 31 5790, CA 54 2911i, CA 69 35876s).
A disubstituted quinoline has been oxidized by sodium chlorite to pyridine dicarboxylic acid, as shown in German Patent No. 945,147 (1956). U.S. Pat. No. 2,586,555 discloses the oxidation of quinoline by perchloric acid to form nicotinic acid, although it is also disclosed that pyridine dicarboxylic acid can be produced. This process, however, requires uneconomically high temperatures, despite the presence of a catalyst.
The above processes have not proven to be commercially feasible. One or more problems attending these processes are the high cost of the reagents, the severe process conditions required, low yield of product, and difficulty in isolating the product from the reaction process. As a consequence, pyridine-2,3-dicarboxylic acid is commercially available only at high cost.
A process which heretofore has been of some commercial significance is that disclosed in German Pat. No. 3,150,005. In that process, a quinoline which must contain substitution in the non-heterocyclic ring by an activating group is oxidized by a chlorate salt. The practical use of this process is limited by the commercial availability of activated quinolines. Such activated quinolines that are commercially available are the hydroxyquinolines, which are prepared by sulfonation of quinoline with subsequent caustic fusion and hydrolysis of the fusion products.
Consequently, there remains a need for a commercially practical process for the preparation of pyridine dicarboxylic acid from more readily available starting compounds.